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Receptor mediated signaling by lysophosphatidic acid and epidermal growth factor in a colon cancer cell line
Author(s) -
Bell Aimee Kristina,
Zhang Zhihong,
Meier Kathryn
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1096.7
Subject(s) - lysophosphatidic acid , epidermal growth factor , pertussis toxin , receptor , epidermal growth factor receptor , microbiology and biotechnology , mapk/erk pathway , biology , signal transduction , tyrosine kinase , fetal bovine serum , growth factor receptor , caco 2 , cholera toxin , cancer research , growth factor , receptor tyrosine kinase , endocrinology , g protein , cell , biochemistry
Lysophosphatidic acid (LPA) is a lipid mediator that promotes proliferation, migration and survival in many types of cancer cells. LPA binds to G protein‐coupled receptors (LPARs). LPA has a well established, but not well understood, relationship with epidermal growth factor (EGF), a peptide growth factor that binds to tyrosine kinase receptors (EGFRs). Our laboratory has shown that bidirectional cross‐talk can occur between LPARs and EGFRs. A better understanding of the interaction between these two receptors is necessary to develop improved anti‐cancer therapeutics. This study addresses the relationship in a colon cancer model. Both LPA and EGF receptors are known to be overexpressed in colon cancer. In the current study, we use Caco‐2 cells, a human source colorectal adenocarcinoma line that shares brush border characteristics with small intestine tissue. The hypothesis addressed was that cross‐talk between LPARs and EGFRs substantially contributes to overall responses to EGF. Serum‐starved Caco‐2 cells were incubated with and without pertussis toxin to block LPA response. Cells were then treated with fetal bovine serum (10%), LPA (10μM), or EGF (100 nM). Whole‐cell extracts were immunoblotted for activated signaling proteins to determine whether inhibition of LPAR attenuates EGFR activation. The results show that serum, LPA, and EGF all activate Erk, p70S6K, and Akt in Caco‐2 cells. Pertussis toxin reduces protein kinase activation in response to all three agonists. These results suggest that Caco‐2 cells are an appropriate model system in which to explore cross‐talk between EGFRs and LPARs.